Abstract: The measurement of low frequency weak signal (MLFWS), especially in complex circumstances, has universal application in contemporary research. In this paper, a high accurate detection system (HADS), used in MLFWS with an amplitude of 0.01 nA or mV below 500 Hz, has been designed, based on the shortcomings of MLFWS including low accuracy, complex procedures, expensive equipment and so on at present. First of all, the noise sources and anti-interference actions of MLFWS in real environments were analyzed theoretically; secondly, HADS, used in MLFWS, was designed, based on the characteristics of MLFWS and anti-interference measures; finally, the performances of HADS were tested by debugging and human-based pulse signal detection experiments. The results demonstrate that HADS could achieve the detection error of less 0.5%, in the MLFWS with amplitude of 0.01 nA or mV below 500 Hz.The signal and noise ratio (SNR)was(60±2 )dB, and root mean square error(RMSE) was less than 5×10^-4, in the measurement of human-based pulse signal. In conclusion, HADS has excellent characteristics, including high accuracy, good anti-interference, stability, practicality, easy operation, low price and so on.